MicroRNA-223 protects neurons from degeneration in experimental autoimmune encephalomyelitis

Morquette, Barbara; Juźwik, Camille A.; Drake, Sienna S.; Charabati, Marc; Zhang, Yang; Lécuyer, Marc-André; Galloway, Dylan A.; Dumas, Aline; Faria, Omar de; Paradis-Isler, Nicolas; Bueno, Mardja; Rambaldi, Isabel; Zandee, Stéphanie; Moore, Craig S.; Bar‐Or, Amit; Vallières, Luc; Prat, Alexandre; Fournier, Alyson E.

doi:10.1093/brain/awz245

Cited by 52 publications

(32 citation statements)

References 78 publications

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“…Without miR-223, retinal function appears to be worsened, whereas both locally and systemically delivered miR-223 mimics led to an improvement in retinal function. This again demonstrates that miR-223 may be required in the preservation of the retinal response, perhaps by promoting microglial homeostatic maintenance (Galloway et al, 2019;Guo et al, 2019), or through neuroprotection and GluR signaling as discussed earlier (Harraz et al, 2012;Morquette et al, 2019). When delivered locally, miR-223 supplementation also protected mice from photoreceptor loss.…”

Section: Delivery Of Mir-223 Mimics Improve Retinal Functionsupporting

confidence: 57%

“…The ERG b-wave was also dampened in miR-223-null photo-oxidative damaged mice, indicating reduced ON-bipolar and Müller cell activity. A potential loss of miR-223-mediated neuroprotection could again have contributed to both of these observations (Harraz et al, 2012;Morquette et al, 2019). These data point to miR-223 having dual protective and damaging roles in the degenerating retina.…”

Section: Dual Roles For Mir-223 In Retinal Degenerationmentioning

confidence: 92%

“…It is possible that reduced C1qa in miR-223-null retinas contributes to altered retinal function in normal conditions; although as C1qa is not a known target of miR-223, this could be occurring through other microglial components that may activate the complement system. Other studies have suggested a role for miR-223 in the neuroprotection of photoreceptors and second-order neurons, showing that the expression of glutamate receptor (GluR) subunits may be regulated by miR-223 (Harraz et al, 2012;Morquette et al, 2019). In particular, GluR2 and NR2B have been identified as potential targets of miR-223 (Harraz et al, 2012), with GluR2 thought to be expressed by bipolar cells housed within the INL (Lin et al, 2012).…”

Section: Mir-223 Is Required For Maintaining Retinal Functionmentioning

confidence: 99%

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MicroRNA-223 Regulates Retinal Function and Inflammation in the Healthy and Degenerating Retina

Fernando

Wong

Das

et al. 2020

Front. Cell Dev. Biol.

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Introduction: MicroRNAs (miRNAs) are small, non-coding RNA molecules that have powerful regulatory properties, with the ability to regulate multiple messenger RNAs (mRNAs) and biological pathways. MicroRNA-223-3p (miR-223) is known to be a critical regulator of the innate immune response, and its dysregulation is thought to play a role in inflammatory disease progression. Despite miR-223 upregulation in numerous neurodegenerative conditions, largely in cells of the myeloid lineage, the role of miR-223 in the retina is relatively unexplored. Here, we investigated miR-223 in the healthy retina and in response to retinal degeneration. Methods: miR-223-null mice were investigated in control and photo-oxidative damageinduced degeneration conditions. Encapsulated miR-223 mimics were intravitreally and intravenously injected into C57BL/6J wild-type mice. Retinal functional responses were measured using electroretinography (ERG), while extracted retinas were investigated by retinal histology (TUNEL and immunohistochemistry) and molecular analysis (qPCR and FACS). Results: Retinal function in miR-223 −/− mice was adversely affected, indicating that miR-223 may be critical in regulating the retinal response. In degeneration, miR-223 was elevated in the retina, circulating serum, and retinal extracellular vesicles. Conversely, retinal microglia and macrophages displayed a downregulation of miR-223. Further, isolated CD11b + inflammatory cells from the retinas and circulation of miR-223-null mice showed an upregulation of pro-inflammatory genes that are critically linked to retinal inflammation and progressive photoreceptor loss. Finally, both local and systemic delivery of miR-223 mimics improved retinal function in mice undergoing retinal degeneration. Conclusion: miR-223 is required for maintaining normal retinal function, as well as regulating inflammation in microglia and macrophages. Further investigations are

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Section: Delivery Of Mir-223 Mimics Improve Retinal Functionsupporting

confidence: 57%

Section: Dual Roles For Mir-223 In Retinal Degenerationmentioning

confidence: 92%

Section: Mir-223 Is Required For Maintaining Retinal Functionmentioning

confidence: 99%

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MicroRNA-223 Regulates Retinal Function and Inflammation in the Healthy and Degenerating Retina

Fernando

Wong

Das

et al. 2020

Front. Cell Dev. Biol.

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“…More in detail, we observed strong and direct correlations (r > 0.5) between let-7b-5p and miR-451a (r = 0.84), miR-223-3p (r = 0.68), miR-92a-3p (r = 0.63) and miR-16-5p (r = 0.54). Interestingly, all these miRNAs have been implicated in MS as crucial regulators of the immune system [54][55][56][57][58][59] and/or CNS homeostasis [55,[60][61][62][63]. Similar considerations can be made about miRNAs that were milder correlated with let-7b-5p (0.4 < r ≤ 0.5), like miR-24-3p and miR-34a-5p, or with the remyelination-related miR-219-3p [36], suggesting that multiple but common cellular sources participate to their release into the CSF [6,64].…”

Section: Let-7b-5p Is a Possible Regulatory Hub Of The Pattern Of Ms-mentioning

confidence: 99%

The microRNA let-7b-5p Is Negatively Associated with Inflammation and Disease Severity in Multiple Sclerosis

Mandolesi

Rizzo

Balletta

et al. 2021

Cells

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The identification of microRNAs in biological fluids for diagnosis and prognosis is receiving great attention in the field of multiple sclerosis (MS) research but it is still in its infancy. In the present study, we observed in a large sample of MS patients that let-7b-5p levels in the cerebrospinal fluid (CSF) were highly correlated with a number of microRNAs implicated in MS, as well as with a variety of inflammation-related protein factors, showing specific expression patterns coherent with let-7b-5p-mediated regulation. Additionally, we found that the CSF let-7b-5p levels were significantly reduced in patients with the progressive MS compared to patients with relapsing-remitting MS and were negatively correlated with characteristic hallmark processes of the two phases of the disease. Indeed, in the non-progressive phase, let-7b-5p inversely associated with both central and peripheral inflammation; whereas, in progressive MS, the CSF levels of let-7b-5p negatively correlated with clinical disability at disease onset and after a follow-up period. Overall, our results uncovered, by the means of a multidisciplinary approach and multiple statistical analyses, a new possible pleiotropic action of let-7b-5p in MS, with potential utility as a biomarker of MS course.

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“…MicroRNAs (miRNAs) are a class of noncoding, single-stranded RNA molecules of approximately 22 nucleotides encoded by endogenous genes that participate in the regulation of posttranscriptional gene expression [5]. To date, 28,645 miRNA molecules have been found in plants, animals, and viruses [6]. Most miRNA genes exist in the genome as a single copy, multiple copies, or in a cluster [7].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-346 inhibits the growth of glioma by directly targeting NFIB

Zhang

et al. 2019

Cancer Cell Int

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BackgroundGlioma is considered one of the most common tumors and has a poor prognosis. Recently, microRNAs (miRNAs) have been reported to be strongly linked to various human tumors including glioma. In this study, we investigated a new anticancer miRNA, miR-346, to determine the effects and mechanism of miR-346 and its downstream target gene NFIB on tumors.MethodsLentivirus transfection, real-time PCR, western blotting, immunohistochemistry, cell proliferation assays, and mouse experiments were used to examine the relationship between miR-346 and its regulation of NFIB in glioma cells.ResultsThe expression of miR-346 was downregulated in glioma cells. Overexpression of miR-346 arrested the cell cycle of glioma cells and inhibited their proliferation in vitro and in vivo. NFIB was a direct target of miR-346, whose expression was reduced by the miRNA. Overexpression of NFIB reversed all tested functions of miR-346.ConclusionmiR-346 inhibited the growth of glioma cells by targeting NFIB and may be a new prognostic and diagnostic biomarker for glioma.

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MicroRNA-223 protects neurons from degeneration in experimental autoimmune encephalomyelitis

Cited by 52 publications

References 78 publications

MicroRNA-223 Regulates Retinal Function and Inflammation in the Healthy and Degenerating Retina

MicroRNA-223 Regulates Retinal Function and Inflammation in the Healthy and Degenerating Retina

The microRNA let-7b-5p Is Negatively Associated with Inflammation and Disease Severity in Multiple Sclerosis

MicroRNA-346 inhibits the growth of glioma by directly targeting NFIB

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